Bilayer Heterogeneous Methacrylated Silk Fibroin Scaffold with Antibacterial and Osteoinductive Functions for Treating Infectious Bone Defects

Infectious bone defects (IBDs) pose a significant clinical challenge due to the simultaneous requirements for effective infection control and robust bone regeneration, and guided bone regeneration (GBR) using multifunctional scaffolds offers a promising therapeutic strategy. Herein, we developed a bilayer hydrogel scaffold (DSHM) based on methacrylated silk fibroin (SilMA) integrated with hydroxyapatite (HA) and minocycline hydrochloride (MH) to address these demands. By precisely optimizing the concentrations of SilMA, photoinitiator, HA, and MH, we engineered a bilayer structure featuring a porous HA-loaded layer (PSH, ∼432.1 μm) to enhance mechanical strength and support osteogenic differentiation and a dense MH-loaded layer (DSM, ∼34.6 μm) to act as a barrier against fibrous tissue ingrowth and provide sustained antibacterial effects. The interface-cross-linked DSHM scaffold exhibited a well-defined heterogeneous architecture, improved mechanical properties, tunable degradation, and excellent biocompatibility. Notably, the DSHM demonstrated synergistic multifunctionality, including inhibition of fibroblast infiltration, promotion of bone tissue regeneration, and effective infection control. Overall, the DSHM scaffold presents a robust approach for the localized and targeted treatment of IBDs, with strong potential for clinical translation.